Synthesis, molecular modeling, and biological evaluation of 1,2,4-triazole derivatives containing pyridine as potential anti-tumor agents

被引：0
作者：
Yan-Bin Zhang
Wen Liu
Yu-Shun Yang
Xiao-Liang Wang
Hai-Liang Zhu
Li-Fei Bai
Xiao-Yang Qiu
机构：
[1] Nanjing University,State Key Laboratory of Pharmaceutical Biotechnology
[2] Jiangsu Institute of Education,School of Life Sciences and Chemistry
[3] Shangqiu Normal University,Department of Chemistry
来源：
Medicinal Chemistry Research | 2013年 / 22卷
关键词：
FAK; 1,2,4-triazole; Anti-tumor activity; Molecular docking;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
There is an accumulating body of experimental evidences validating focal adhesion kinase (FAK) as a therapeutic target and offering opportunities for anti-tumor drug development. In present study, we sought to synthesize twenty-eight potential FAK inhibitors as anti-tumor agents based on 1,2,4-triazole skeleton. The bioassay assays demonstrated that compounds 3e and 6j showed the most potent activity, 3e inhibited the growth of HCT116 and HepG2 cell lines with IC50 values of 8.17 and 7.04 μM, while compound 6j showed the most potent biological activity against HCT116 cell line (IC50 = 1.99 μM). Besides, compound 6j also exhibited significant FAK inhibitory activity (IC50 = 2.41 μM). The results of flow cytometry and western-blot assay demonstrated that compounds 3e and 6j possessed good anti-proliferative activity. Docking simulations were performed to position compounds 3e and 6j into the active site of FAK to determine the probable binding model.
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页码：3193 / 3203
页数：10
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